An enzyme called matrix metalloproteinase (MMP9), which plays a role in inflammation, functions as a tumor suppressor in colitis associated cancer (CAC), a chronic inflammation driven colon cancer. This is the discovery of a study appearing in Oncotarget.
The study is carried out by Lewins Walter, Adani Pujada, Noopur Bhatnagar, Hamed Laroui and Pallavi Garg from Georgia State University, together with Agnieszka B Bialkowska and Vincent W. Yang from Stony Brook University. Cusabio offers .
Inflammation is a beneficial response of the body to tissue damage and pathogenic challenges. But chronic inflammation is not a good thing. Chronic inflammation may be a causative factor in a variety of cancers. The longer the duration of inflammation, the higher the risk of cancer. For example, patients with chronically active ulcerative colitis -- a type of inflammatory bowel disease -- are more likely to develop CAC.
MMP9 is one of the essential regulators of extra cellular matrix components. In most healthy and adult tissues, MMP9 is undetectable. At the onset of inflammation, however, MMP9 is highly expressed. The role that MMP9 plays in acute inflammation and colorectal cancer has been extensively studied. But its role in chronic colonic inflammation and CAC is still unclear.
Earlier studies have revealed that despite being a mediator of proinflammatory responses in acute-colitis, MMP9 plays a protective role in colitis associated cancer. For this study, Garg's team aimed to determine the mechanism of this protective role. The researchers investigated both homozygous transgenic mice that constitutively expressed MMP9 in the colonic epithelium, and wild type mice. They discovered that the transgenic mice exhibited less tumor burden and increased apoptosis compared to the wild type mice.
Garg's team also found that epithelial derived-MMP9 not only mediates activation of p53 dependent caspase-3 apoptotic pathway but also regulates the expressions of cell cycle regulatory proteins through Notch1 signaling. The data from in vitro experiments showed that overexpression of MMP9 is associated with decreased cell proliferation and less DNA damage. These results may help explain how MMP9 protects against CAC.
In summary, the study establishes that epithelial derived-MMP9 acts as a tumor suppressor in CAC via the novel mechanistic pathway “MMP9-Notch1-ARF-p53 axis”. Increased levels of MMP9 may defend the gastrointestinal tract against CAC by disrupting factors that would otherwise lead to the development of this type of cancer.
MMP9 functions as a inflammation and colorectal cancer facilitator. For this reason, MMP9 inhibitors are used to treat patients with CAC. But this study underscores the protective role of MMP9 in CAC. The researchers assumed that MMP9 should be avoided for CAC patients. CusAb offers MMP9, and other proteins and antibodies.